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Telomeres: cancer to human aging
Sheila A Stewart1, Robert A Weinberg
1Departments of Cell Biology and Physiology and of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. sheila.stewart@cellbiology.wustl.edu
Annual Review of Cell and Developmental Biology
|July 11, 2006
Summary
Mammalian cell senescence and crisis limit tumor formation by regulating telomeres. Escaping these processes via cell immortalization is crucial for cancer development, highlighting telomere maintenance
Area of Science:
- Cell biology
- Genetics
- Cancer research
Background:
- Cellular senescence and crisis phenotypes limit mammalian cell proliferation, suggesting in vivo tumor suppression roles.
- Telomeres, protective chromosome end structures, are key regulators; erosion below a critical length triggers crisis.
- Senescence is also induced by cellular stresses and telomeric DNA dysfunction, with a complex relationship to telomere length.
Purpose of the Study:
- To explore the roles of telomeres in regulating cell senescence and crisis.
- To discuss mechanisms by which cells escape senescence and crisis, leading to immortalization.
- To examine the influence of telomere maintenance and dysfunction on aging and carcinogenesis.
Main Methods:
- Review of existing literature on telomere biology, senescence, and crisis.
- Analysis of the molecular pathways regulating telomere maintenance and cell cycle control (Rb, p53).
- Discussion of the link between cell immortalization and the tumorigenic phenotype.
Main Results:
- Telomere length critically influences cell fate, triggering crisis upon critical erosion.
- Senescence can be initiated by various stresses and telomere dysfunction.
- Inactivation of tumor suppressors (Rb, p53) or activation of telomere maintenance allows cells to bypass senescence/crisis.
Conclusions:
- Telomere monitoring and maintenance are crucial biological functions.
- Loss of telomere integrity contributes to aging and carcinogenesis.
- Cell immortalization, often involving telomere maintenance, is a key step in human cancer development.